The primary objective of this proposal is to complete the improvements in the isolation of purified islets in the dog that have recently permitted successful autotransplantation to permit studies of immunoalteration that could permit transplantation without immunosuppression. A new method of isolated islet preparation has been developed that includes a predigestion perfusion of the gland followed by preparation of isolated islets by an auto-isolator. Methods of purification will include density gradients and in vitro culture. Autotransplantation and allotransplantation will be done examining a numer of methods of immunoalteration. Successful completion of these studies will permit evaluation of the best method to apply for clinical trils once the safety and efficacy have been demonstrated.